Numerous studies have reported altered OXT signaling in the brain following both acute and chronic exposure to alcohol and drugs. For example, studies in rodents have shown that chronic exposure to nicotine, methamphetamine, cocaine, and morphine generally result in an upregulation of OXTR binding and decrease in OXT peptide content in various brain regions (Georgiou et al., 2015, Zanos et al., 2016, Zanos et al., 2014). Repeated exposure to cocaine in rats produced a reduction in OXT plasma concentrations, accompanied by reduced OXT content in hypothalamus and hippocampus, which may reflect decreased OXT synthesis and release (Sarnyai et al., 1992). Chronic methamphetamine administration produced an upregulation in OXT receptor density in the amygdala and hypothalamus (Zanos et al., 2014). Marked alterations in OXT peptide and/or synthesis have also been reported following opiate administration. In mice, repeated exposure to morphine resulted in decreased OXT levels in the hippocampus (Kovacs et al., 1987). Chronic morphine treatment in rats produced region-specific alterations in brain OXT expression, with decreased Oxt mRNA in the hypothalamus (SON) and NAc and increased mRNA expression in the VTA
